e20042 Background: The purpose of this sub study was to identify peripheral blood biomarkers associated with the therapeutic effect of immunotherapy with dendritic cell vaccine in patients with metastatic melanoma (MM). Methods: Patients (pts) with low disease burden achieved disease control after two cycles of chemo (cisplatine, vinbalstie, DTIC) were randomized dendritic cell vaccine (DC) or three cycles of chemo. Vaccination schedule consisted of 5 subcutaneous injections of dendritic cell (DC) vaccine (2×106 cells pulsed with autologous lysate) with 14 days intervals. S100B level, LDH level, and peripheral blood lymphocytes immune phenotype were assessed before treatment, after two cycles of chemo and after each vaccination cycle. Results: 104 pts were included in the study, 30 pts were randomized to DC arm, 29 pts were randomized to continue chemo. In pts with rapid disease progression baseline serum S100b level was significantly higher compared to patients with objective response or stable disease (0.874±1.15 mcg/L vs. 0.361±0.66 mcg/L, P=0.002). Similar results were found for baseline serum LDH level (559.8±469.7 U/L vs. 412.5±184.4 U/L, P=0.005) and serum S100b level after 2 cycles of chemo (0.688±0.855 mcg/L vs. 0.187±0,29 mcg/L, P<0.001). Contrary, baseline CD3+HLA-DR+ and CD4+CD25+ lymphocytes levels after 2 cycles of chemo were significantly higher in pts with disease control (11.9±8.9% vs. 8.9±5.3%, P=0.047 and 14.4±8.3% vs. 11.3±5.5%, P=0.036 respectively).In pts randomized to DC arm following markers were associated with long lasting objective response or stable disease course (>6 months): lower baseline S100b level (0.133±0.120 mcg/L vs. 0.445±0.406 mcg/L, P=0.014), lower S100b level after 2 cycles of chemo (0.105±0.095 mcg/L vs. 0.255±0.154 mcg/L, P=0.048), higher proportion of active CD8+lymphocytes prior to vaccination (74.7±3.6% vs. 51.7±14.2%, P=0.05); and more prominent increase of NK-cells CD3-CD16+CD56+ from baseline (increase in 76.5%±41.12% vs. 4.5±28.8%, P=0.01). Conclusions: Biochemical and immunological markers may be helpful when selecting patients with metastatic melanoma for immunotherapy with dendritic cell vaccine.
The effects of minocycline on hippocampus in lithium-pilocarpine induced status epilepticus in rat: relations with microglial/astrocytic activation and serum s100b level
